Association of HLA–DR4 with a more progressive disease course in patients with rheumatoid arthritis. Results of a followup study

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Abstract
The association between HLA–DR antigens and rheumatoid arthritis (RA) was investigated in a wellcharacterized cohort of RA patients who were followed from the beginning of the disease (mean followup 6 years). The frequencies of HLA–DR antigens in patients with possible or probable RA (n = 49) were similar to those in controls. In patients with definite RA (n = 134), the frequencies of DR1, DR4, and DRw53 were increased, whereas the frequencies of DR2, DR3, DRw6, DRw13, and DRw52 were decreased, compared with controls. Comparison of HLA–DR frequencies in patients with definite RA subclassified according to the severity of the disease at the end of the followup period revealed a difference only in the frequency of DR4, which was increased in patients with progressive RA (59.2%) compared with those who had mild RA (34.8%). Further analysis showed that, compared with DR4‐negative RA patients, DR4‐positive patients had more swollen joints, higher scores on the Ritchie articular index, the Health Assessment Questionnaire, and the Steinbrocker functional classification, more radiologic abnormalities, and more use of second‐line drugs. Also, the rate of progression of radiologic abnormalities, functional classification, and use of second‐line drugs was higher in DR4‐positive patients. We conclude that DR4 is associated with a more severe disease course, and is a prognostic marker in early RA.